Controlled-release dosage forms are designed to reduce drug-dosing frequency and to reduce fluctuation in plasma drug concentration, providing a more uniform therapeutic effect. Less frequent dosing is more convenient and may improve patient compliance. These dosage forms are suitable for drugs that otherwise require frequent dosing because elimination half-life and duration of effect are short.
Man-made controlled release dosage forms, such as hydrogels and solid polymeric microspheres, usually rely on drug release mechanisms that are based on passive diffusion, polymer degradation or passive diffusion coupled with polymer degradation. Examples of these systems include polyester microspheres or alginate hydrogels.
On the other hand, nature's way of devising controlled release dosage forms is based on principles of biological specificity. A known example to this is the biomolecular interactions between heparin/heparan sulfate and heparin-binding peptides, e.g. growth factors. These interactions form a depot for growth factor storage in the tissues. Upon tissue injury, the growth factors are released and induce processes associated with wound healing.
For years, we and others have been investigating the use of alginate hydrogels for the controlled delivery of drugs and as scaffolds for tissue engineering.
Alginate is a polysaccharide derived from brown seaweed. It is an anionic polysaccharide composed of uronic acids (guluronic (G) and mannuronic (M) acids) that undergoes gelation in the presence of bivalent cations, such as Ca2+ and Ba2+. In the pharmaceutical/medicinal fields, it is used successfully as encapsulation material, mostly for cells (bacterial, plant and mammalian cells). For molecules, it is much less effective, and even macromolecules in size of 250 kDa are rapidly released from alginate hydrogel systems. In particular, biological molecules of interest such as cytokines, growth factors, with sizes ranging between 5 to 100 kDa, are rapidly released.
Thus, there is a need for modification/s in polysaccharides such as alginate for their use in the controlled delivery of drugs. Recently, the inventors disclosed in an abstract that alginate sulfate interacts with basic fibroblast growth factor (bFGF) and delivers bFGF in a controlled manner (Freeman et al., 2004).